Phosphorylcholine group-containing chemical compounds are used as surface treatment agents to improve biocompatibility and such. For example, in Patent document 1 they are used as surface treatment agents for diagnostic equipment and contact lenses for the purpose of decreasing the deposition of proteins and cells.
In Patent document 1, the phosphorylcholine group-containing chemical compound used as a surface treatment agent is the compound of formula (I) in claim 1 of the patent. This compound is obtained from a reaction of the carboxyl phosphorylcholine derivative shown in formula (V) in the right lower column of page 5. That is, an appropriate compound chosen from the carboxyl phosphorylcholine derivatives of general formula (V) is used.
The appropriate carboxyl phosphorylcholine derivatives represented by formula (V) are compounds having chemical structures that are considered usable as a source material compound to manufacture the compound of surface treatment agent formula (I) and they are shown in the form of a general formula. In the right lower column of page 6 of the document, the following formula (4) is shown as the compound having the simplest structure that meets this general formula. From this it can be understood that the compound having the simplest structure that meets formula (V) is the most useful. This reaction formula (6) describes the compound of formula (4) as an ideal compound conceivable for use in a reaction to manufacture the compound of formula (I), a surface treatment agent; however, this is not an existing compound actually synthesized in Patent document 1: this is not a prior art compound actually synthesized.(CH3)3NCH2CH2PO4C2H4COOH  (4)
For the carboxyl phosphorylcholine having a simple structure that is a prior art compound included in general formula (V), the compound of the following formula (5) is reported to have been bought from Molecular Probe Inc. (Non-Patent document 1). However, Non-Patent document 1 does not mention specific synthesis examples, and no corresponding chemical compound has been found on Molecular Probe's website.(CH3)3NCH2CH2PO4C5H10COOH   (5)
However, the compound of formula (5) is not sufficient for endowing these materials with maximum biocompatibility because of the spacer (C6H10 portion) that binds the phosphorylcholine group portion, which is involved in biocompatibility, and the material to be treated.
With regards to methods for manufacturing phosphorylcholine compounds, several synthesis examples have been proposed (Patent documents 2-4, Non-patent documents 2).
However, these methods use phosphorus oxychloride for the starting substance and therefore have a shortcoming in that they are cumbersome methods.
For example, the reaction must be carried out under strict moisture-free conditions. Therefore, moisture in the reaction atmosphere must be removed as well.
Also, the purification process for the target phosphorylcholine compound is cumbersome and its purification is quite difficult. The reaction yield is low as well.
Furthermore, an organic solvent is used for the reaction solvent, which means purification of the reaction solvent (moisture removal) has to be carried out strictly and there are environmental problems due to the use of the organic solvent.
As described thus far, conventional methods to manufacture phosphorylcholine compounds that use phosphorus oxychloride as the starting substance have many problems as an industrial manufacturing method.
Patent Document 1: Japanese Patent Laid-Open H5-505121 bulletin
Patent Document 2: Japanese Patent Laid-Open S63-222183 bulletin
Patent Document 3: Japanese Patent Laid-Open H7-10892 bulletin
Patent Document 4: U.S. Pat. No. 5,648,442 bulletin
Non-patent document 1: Journal of Protein Chemistry, 117 (10) 1 1991
Non-patent document 2: Polymer Journal, vol. 22 355-360 (1990)